Analogs of the thyroid hormones will be synthesized and these will be tested in vivo and in vitro in order to establish the molecular characteristics responsible for selective hormonal effects. In vitro tests include measurement of relative binding affinities to the plasma protein, thyroxine-binding prealbumin (TBPA), and to hormone receptor preparations from rat liver cell nuclei. The well characterized molecular interactions of analogs with TBPA will be used to define similarities and differences between TBPA and the poorly characterized nuclear receptor. In vivo tests include the rat antigoiter assay and studies of the transplacental developmental effects of selected analogs on the fetus of the rat, rabbit and sheep. Computer graphics will be used to visualize analog-TBPA interactions, to develop a model of the nuclear receptor, and to guide the design of new analogs that might possess selective hormonal properties, including those of a hormone antagonist.